Ether preservation



United States Patent ETHER PRESERVATION No Drawing. Application July 19, 1954,

Serial No. 444,393

11 Claims. (Cl. 260-6115) i This invention relates to ether preservation, and more particularly to the preservation of ether by means of cer-. tain 1,10-phenanthroline preservative compounds.

Briefly, this invention relates to a composition comprising ether and a preservative compound selected from the group consisting of LIO-phenanthroline, cupric 1,10- phenanthroline, ferrous 1,10-phenanthroline and lead 1,10-phenanthroline. The invention also relates to the method of preserving ether which comprises dissolving therein a preservative compound selected from the abovenoted group.

Among the objects of the invention may be noted the provision of improved means of preserving ether against decomposition; the provision of such means which are effective in minute quantities to preserve ether; and the provision of means of the character described which preserve ether for relatively long periods of time; Other objects and features will be. in part apparent and in part pointed out hereinafter.

The invention accordingly comprises the products and methods hereinafter described, the scope of the invention being indicated in the following claims.

Diethyl ether in untreated tin cans, within a short time following its manufacture, may acquire sufficient decomposition products to make it fail to pass the United States Pharmacopoeias rigorous requirements for ether intended for anesthesia. In recognition of these properties of ether, the Pharmacopoeia requires that ether for anesthesia be packed in tight containers of not more than 3 kg. capacity and that it be used within twenty four hours after removal from the original container. Peroxide and aldehyde impurities are particularly objectionable in anesthetic ether, and indeed are limited to the merest traces by the specification of the United States Pharmacopoeia. Once started, the formation of peroxides may increase through auto-oxidation. Heat, light, air and catalytically active surfaces inside the container influence the formation of ether peroxides. The effects of these factors on the formation of peroxide impurities may be considerably minimized by forming on the cans inner surface an adherent layer of tin oxide or a coating of metallic copper. Such expedients, however, are not entirely satisfactory. The best results have been obtained with a container having a copper-tin oxide coating on the inside surface, as described and claimed in our U. S. Patent No. 2,587,744, issued March 4, 1952. Another expedient which has been employed is the addition of a preservative to the ether which prevents or inhibits peroxide formation. Hydroquinone and diphenylamine are well-known preservatives; but these compounds possess only limited usefulness.

In accordance with the present invention, 1,10- phenanthroline and certain 1,10-phenanthroline metal organic complexes have been found which exhibit an improved preserving action on ether. When dissolved in ether in minute amounts, they are effective in preventing, inhibiting or delaying the formation of peroxides, thereby prolonging the keeping time Ice of ether following manufacture. The use of these preservative compounds in conjunction with treated or coated containers, such as mentioned above, is particularly advantageous and considerably increases the stability of ether in storage. In addition to 1,10-phenanthroline, the particular 1,10-phenanthroline salts which have been found effective in preserving ether are the cupric, ferrous and lead salts.

These 1,1.0-phenanthroline preservative compounds of this invention are more effective than hydroquinone to increase the keeping time of ether even at concentrations one-tenth to one-hundredth that of hydroquinone. All the compounds of the present invention exhibit improved preserving action at a concentration of only 10* molar or less when compared with hydroquinone at ten times this concentration (10* molar). Furthermore, when employed in conjunction with treated containers having an interior adherent coating of copper-tin oxide or lacquer varnish, still smaller concentrations of these preservative compounds are effective.

The following examples illustrate the invention.

Example 1 The preservative action of these compounds upon ether was demonstrated by an accelerated aging test of the compositions of the present invention under conditions which favor the rapid spoilage of ether, i. e., contact with a polished tin surface and shaking it at a temperature of F. for sixteen hours. The preservatives to be tested were dissolved in freshly distilled anhydrous (absolute) ether, initially containing less than 0.05 p. p. m. peroxide and less than 2-3 p. p. m. aldehyde, and made up to the desired concentration. By this test, the relative eflectiveness of various preservatives and other methods of preserving ether can be determined.

At the end of the sixteen-hour test period the ether was tested for the amount of peroxide and aldehyde it contained. If the sample was found to contain more than 0.2 part per million peroxide (the U. S. P. limit corresponds to about 0.5 p. p. m.) or over 3 p. p. m. aldehyde as acetaldehyde (the U. S. P. limit corresponds to slightly over 13 p. p. m.) it was considered to have failed in the test. In carrying out the tests, the preservative is added to 18 ml. of freshly distilled ether in a tin vessel half full, the inner surfaces of which have been mildly abraded to remove surface film or tarnish, and the vessels shaken 16 hours at a temperature of 100 F. The well-known ammonium thiocyanate-ferrous sulphate reaction was used with a set of standard colors to determine the peroxides, and Nesslers reagent with color standards was used to estimate the aldehyde.

In the case of hydroquinone, it was found that, at a concentration of 10* molar (ll mg./l.), twenty out of twenty-one samples passed the accelerated aging test with respect to peroxide, whereas, at a concentration of 10- molar (1.1 mg./l.) only ten out of fifty-two samples passed. The color test for aldehyde could not be read at 10* molar because hydroquinone at this concentration interferes with the test; but at a concentration of 1()- molar nearly half of the samples failed. In each series of tests, samples of ether containing no preservatives were included to be certain that the conditions were such that untreated ether would spoil during the sixteen-hour test period.

Three samples of ether containing diphenylamine at a concentration of 10" molar (1.7 mg./l.) and three samples containing the same compound at a concentration of 10* molar (0.17 mg./l.) were also prepared and tested. All six samples failed both the peroxide and aldehyde tests.

Three samples of ether containing 1,10-phenanthroline at a concentration of 10 molar (1.80 mg./l.) and three 3 at 10- (0.180 mg./l.) were tested by the above procedure. At the end of the accelerated aging test it was found that all three samples at a concentration of 10 molar passed both the aldehyde and peroxide tests, while at a concentration of 10* molar two samples passed the aldehyde and peroxide tests.

. Example 2 Example 1 was repeated except that three samples of ether containing cupric 1,10-phenanthroline at a concentration of 5X10 molar (2.12 mg./l.) and three samples at a concentration of 5 l0 molar (0.212 mg./l.) were employed. At both these concentrations all samples passed both the aldehyde and peroxide tests.

Example 3 Example 1 was repeated except that three samples of ether containing lead 1,10-phenanthroline at a concentration of 5 X l molar (2.83 mg./l.) and three samples at a concentration of molar (0.283 mg./l.) were'employed. At a concentration of 5 10-- molar, all three samples passed both the aldehyde and peroxide tests, while at a concentration of 5 10 all samples passed the aldehyde test and two samples passed the peroxide test.

Example 4 Example 1 was repeated except that three samples of ether containing ferrous LIO-phenanthroline at a concentration of 5 10 (2.07 mg./l.) were employed. All samples passed both the aldehyde and peroxide tests.

Thus, the ether preservatives of the present invention when tested according to the accelerated aging tests are many times (e. g., ten to one hundred) more efiective in preserving ether than hydroquinone as determined by standards higher than those required by the U. S. Pharmocopoeia. Moreover, when the preservative compounds of this invention are employed in conjunction with treated containers such as a copper-tin oxide coated can, for example, concentrations even smaller than those used in the foregoing examples are effective to preserve ether for extended periods of time.

In view of the above, it will be seen that the several ob- As various changes could be made in the above methods and products without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

We claim:

1. A composition comprising ether and a preservative compound selected from the group consisting of 1,10- phenanthroline, cupric 1,10-phenanthroline, ferrous 1,10- phenanthroline and lead 1,10-phenanthroline.

2. A composition comprising ether and 1,10-phenanthroline.

3. A composition comprising ether and cupric 1,10-

phenanthroline.

4. A composition comprising ether and ferrous 1,10- phenanthroline.

5. A composition comprising ether and lead 1,10- phenanthroline.

6. The method of preserving ether which comprises dissolving therein a compound selected from the group consisting of 1,10-phenanthroline, cupric LID-phenanthroline, ferrous 1,10-phenanthroline and lead 1,10- phenanthroline.

7. The method of preserving ether which comprises confining in an air-tight container ether having dissolved therein a compound selected from the group consisting of 1,10-phenanthroline, cupric 1,10-phenanthroline, ferrous 1,10-phenanthroline and lead 1,10-phenanthroline.

8. The method of preserving ether which comprises confining in an air-tight container ether having dissolved therein LID-phenanthroline.

9. The method of preserving ether which comprises confining in an air-tight container ether having dissolved therein cupric 1,10-phenanthroline.

10. The method of preserving ether which comprises confining in an air-tight container ether having dissolved therein ferrous 1,10-phenanthroline.

11. The method of preserving ether which comprises I confining in an air-tight container ether having dissolved jects of the invention are achieved and other advantageous results attained.

therein lead 1,10-phenanthroline.

No references cited. 

1. A COMPOSITION COMPRISING ETHER AND A PRESEVATIVE COMPOUND SELECTED FROM THE GROUP CONSISTING OF 1,10PHENANTHROLINE, CUPRIC 1,10-PHENANTHROLINE, FERROUS 1-10PHENANTHROLINE AND LEAD 1,10-PHENANTHROLINE. 